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PURPOSE: To evaluate the 12-month outcomes of a novel posterior small incision sub-tenon ab interno technique of XEN stent insertion (‘Semi-open’). METHOD: Consecutive eyes underwent XEN stent insertion with the Semi-open technique by two surgeons between 1st July 2018 and 30th September 2019. All cases received subconjunctival injection of 0.1 mL of mitomycin C 0.2 mg/mL. Eyes with primary open angle glaucoma (OAG), secondary OAG or pseudophakic primary angle closure glaucoma (PACG) were included. Exclusion criteria were phakic PACG, uveitic or neovascular glaucoma and postoperative follow-up

Purpose This study examines the short-term uptake, compliance, and performance of a tablet device used for home monitoring of visual field (VF-Home) by glaucoma patients. Design Single-center, observational, longitudinal, compliance study. Methods Participants who were glaucoma suspects or had stable glaucoma in at least one eye were recruited during a regular clinic review. Baseline in-clinic visual field (VF) was recorded with the Humphrey Field Analyser (HFA, SITA standard) and repeated at 6 months. Participants were tasked with performing 6 VF examinations from home, at weekly intervals, using a loaned iPad tablet. Uptake was defined as returning at least 1 test from home. Reliability and global indices from VF-Home were compared to in-clinic outcomes. Data are shown as either mean ± [standard deviation] or median [quartile 1-3 range], and group comparisons were achieved with bootstrap. Results We recruited 186 eyes of 101 participants. VF-Home uptake was excellent, with 88% of participants successfully completing ≥1 home examination and 69% completing all 6 examinations. The median duration between tests was 7.0 [7.0-8.0] days. Barriers to uptake and compliance involved information technology (IT) logistical reasons, lack of motivation, or competing life demands. VF-Home gave greater fixation loss but a similar level of False Positives (FP) as the HFA. A high correlation was found for the mean defect between in-clinic and at-home outcomes (R = 0.85). Conclusions VF-Home can return a high level of short-term compliance and results comparable to those found by in-clinic testing. IT logistical reasons and lack of motivation are barriers to uptake and compliance.

Diagnosis of glaucoma requires more than the optic nerve head (ONH) evaluation findings alone, but ONH assessment is crucial to detection of glaucoma, assessment of severity, and monitoring for disease progression. Objective assessment of the ONH must be done independent of other clinical features. This chapter explores the process of examining the disc for glaucoma, where errors may occur, and strategies to avoid them.

Background The refractive outcomes of glaucoma surgeries, particularly their effect on astigmatism, are incompletely understood. Main body Trabeculectomy is associated with a considerable amount of with-the-rule astigmatic change in the immediate postoperative period. This is followed by a gradual against-the-rule shift. These changes are altered with the use of mitomycin C (MMC). Non-penetrating surgery such as deep sclerectomy is also associated with a similar or smaller degree of induced astigmatism. Minimally invasive glaucoma surgery appears to be astigmatically neutral. There is no clear evidence regarding refractive outcomes of glaucoma drainage device surgery. Conclusions Induced astigmatism may account for a reduction in unaided visual acuity in the early postoperative period following a successful trabeculectomy. These changes appear to stabilise at 3 months, and it would be prudent to defer the prescription of new glasses until this time. If sequential cataract surgery is to be performed, toric intraocular lenses can be a useful option for astigmatic correction.

Purpose: To report here a case of uncontrolled glaucoma during third-trimester of pregnancy that was treated successfully with bilateral Xen gel stent insertion. Observations: A 35-year-old woman presented during the third trimester of pregnancy with bilateral uncontrolled primary open angle glaucoma. Her disc examination and visual fields were consistent with advanced glaucoma. After failed Selective Laser Trabeculoplasty and maximal medical treatment, including Acetazolamide, she was treated with bilateral consecutive Xen stent surgery with successful control of her intraocular pressure. Conclusions and Importance: The use of Xen implant may have advantages over traditional trabeculectomy, especially during pregnancy, as the procedure is shorter, with less dependence on on-table antimetabolite and being minimally invasive with sparing of the conjunctiva. Keywords: Xen gel stent, Glaucoma in pregnancy

PURPOSE: To establish the medium-term repeatability of the iPad perimetry app Melbourne Rapid Fields (MRF) compared to Humphrey Field Analyzer (HFA) 24-2 SITA-standard and SITA-fast programs. DESIGN: Multicenter longitudinal observational clinical study. METHODS: Sixty patients (stable glaucoma/ocular hypertension/glaucoma suspects) were recruited into a 6-month longitudinal clinical study with visits planned at baseline and at 2, 4, and 6 months. At each visit patients undertook visual field assessment using the MRF perimetry application and either HFA SITA-fast (n = 21) or SITA-standard (n = 39). The primary outcome measure was the association and repeatability of mean deviation (MD) for the MRF and HFA tests. Secondary measures were the point-wise threshold and repeatability for each test, as well as test time. RESULTS: MRF was similar to SITA-fast in speed and significantly faster than SITA-standard (MRF 4.6 ± 0.1 minutes vs SITA-fast 4.3 ± 0.2 minutes vs SITA-standard 6.2 ± 0.1 minutes, P < .001). Intraclass correlation coefficients (ICC) between MRF and SITA-fast for MD at the 4 visits ranged from 0.71 to 0.88. ICC values between MRF and SITA-standard for MD ranged from 0.81 to 0.90. Repeatability of MRF MD outcomes was excellent, with ICC for baseline and the 6-month visit being 0.98 (95% confidence interval: 0.96-0.99). In comparison, ICC at 6-month retest for SITA-fast was 0.95 and SITA-standard 0.93. Fewer points changed with the MRF, although for those that did, the MRF gave greater point-wise variability than did the SITA tests. CONCLUSIONS: MRF correlated strongly with HFA across 4 visits over a 6-month period, and has good test-retest reliability. MRF is suitable for monitoring visual fields in settings where conventional perimetry is not readily accessible.

Purpose To evaluate the use of smartphone-based virtual reality to objectively assess activity limitation in glaucoma. Methods Cross-sectional study of 93 patients (54 mild, 22 moderate, 17 severe glaucoma). Sociodemographics, visual parameters, Glaucoma Activity Limitation-9 and Visual Function Questionnaire - Utility Index (VFQ-UI) were collected. Mean age was 67.4 ± 13.2 years; 52.7% were male; 65.6% were driving. A smartphone placed inside virtual reality goggles was used to administer the Virtual Reality Glaucoma Visual Function Test (VR-GVFT) to participants, consisting of three parts: stationary, moving ball, driving. Rasch analysis and classical validity tests were conducted to assess performance of VR-GVFT. Results Twenty-four of 28 stationary test items showed acceptable fit to the Rasch model (person separation 3.02, targeting 0). Eleven of 12 moving ball test items showed acceptable fit (person separation 3.05, targeting 0). No driving test items showed acceptable fit. Stationary test person scores showed good criterion validity, differentiating between glaucoma severity groups (P = 0.014); modest convergence validity, with mild to moderate correlation with VFQ-UI, better eye (BE) mean deviation, BE pattern deviation, BE central scotoma, worse eye (WE) visual acuity, and contrast sensitivity (CS) in both eyes (R = 0.243-0.381); and suboptimal divergent validity. Multivariate analysis showed that lower WE CS (P = 0.044) and greater age (P = 0.009) were associated with worse stationary test person scores. Conclusions Smartphone-based virtual reality may be a portable objective simulation test of activity limitation related to glaucomatous visual loss. Translational relevance The use of simulated virtual environments could help better understand the activity limitations that affect patients with glaucoma.

We report a case series of three patients with previous trabeculectomies who developed elevated intraocular pressure (IOP) in the immediate postoperative period after routine Descemet stripping automated endothelial keratoplasty (DSAEK). All patients had functioning trabeculectomies preoperatively, and developed elevated IOP between 41 and 69 mm Hg within 24 hours following DSAEK surgery. The IOP was successfully controlled in all patients with topical IOP-lowering medications and oral acetazolamide, with the addition of ocular massage and release of aqueous for two patients. Thereafter, all patients maintained well-controlled IOPs. Patients with trabeculectomies should be followed-up closely immediately after DSAEK to monitor for raised IOP. The mechanism for this pressure rise is uncertain, but may involve air in the trabeculectomy sclerostomy or bleb resulting in blockage of aqueous flow. How to cite this article: Sheales MPH, Chan E, Ang GS, Kong YXG. Elevated Intraocular Pressure after Descemet Stripping Automated Endothelial Keratoplasty in Patients with a Trabeculectomy: A Case Series. J Curr Glaucoma Pract 2015;9(3):100-103.

Background In the assessment of a pituitary mass, objective visual field testing represents a valuable means of evaluating mass effect, and thus in deciding whether surgical management is warranted. Case presentation In this vignette, we describe a 73 year-old lady who presented with a three-week history of frontal headache, and ‘blurriness’ in the left side of her vision, due to a WHO grade III anaplastic haemangiopericytoma compressing the optic chiasm. We report how timely investigations, including an iPad-based visual field test (Melbourne Rapid Field, (MRF)) conducted at the bedside aided swift and appropriate management of the patient. Conclusions We envisage such a test having a role in assessing bed-bound patients in hospital where access to formal visual field testing is difficult, or indeed in rapid testing of visual fields at the bedside to screen for post-operative complications, such as haematoma.

Purpose To evaluate the accuracy and efficiency of Visual Fields Easy (VFE), a free iPad app, for performing suprathreshold perimetric screening. Design Prospective, cross-sectional validation study. Methods We performed screening visual fields using a calibrated iPad 2 with the VFE application on 206 subjects (411 eyes): 210 normal (NL), 183 glaucoma (GL), and 18 diabetic retinopathy (DR) at Tilganga Institute of Ophthalmology, Kathmandu, Nepal. We correlated the results with a Humphrey Field Analyzer using 24-2 SITA Standard tests on 373 of these eyes (198 NL, 160 GL, 15 DR). Results The number of missed locations on the VFE correlated with mean deviation (MD, r = 0.79), pattern standard deviation (PSD, r = 0.60), and number of locations that were worse than the 95% confidence limits for total deviation (r = 0.51) and pattern deviation (r = 0.68) using SITA Standard. iPad suprathreshold perimetry was able to detect most visual field deficits with moderate (MD of −6 to −12 dB) and advanced (MD worse than −12 dB) loss, but had greater difficulty in detecting early (MD better than −6 dB) loss, primarily owing to an elevated false-positive response rate. The average time to perform the Visual Fields Easy test was 3 minutes, 18 seconds (standard deviation = 16.88 seconds). Discussion The Visual Fields Easy test procedure is a portable, fast, effective procedure for detecting moderate and advanced visual field loss. Improvements are currently underway to monitor eye and head tracking during testing, reduce testing time, improve performance, and eliminate the need to touch the video screen surface.

Purpose We hypothesize that: (1) Anterior chamber depth (ACD) is correlated with the relative anteroposterior position of the pupillary image, as viewed from the temporal side. (2) Such a correlation may be used as a simple quantitative tool for estimation of ACD. Methods Two hundred sixty-six phakic eyes had lateral digital photographs taken from the temporal side, perpendicular to the visual axis, and underwent optical biometry (Nidek AL scanner). The relative anteroposterior position of the pupillary image was expressed using the ratio between: (1) lateral photographic temporal limbus to pupil distance (“E”) and (2) lateral photographic temporal limbus to cornea distance (“Z”). In the first chronological half of patients (Correlation Series), E:Z ratio (EZR) was correlated with optical biometric ACD. The correlation equation was then used to predict ACD in the second half of patients (Prediction Series) and compared to their biometric ACD for agreement analysis. Results A strong linear correlation was found between EZR and ACD, R = −0.91, R2 = 0.81. Bland-Altman analysis showed good agreement between predicted ACD using this method and the optical biometric ACD. The mean error was −0.013 mm (range −0.377 to 0.336 mm), standard deviation 0.166 mm. The 95% limits of agreement were ±0.33 mm. Conclusions Lateral digital photography and EZR calculation is a novel method to quantitatively estimate ACD, requiring minimal equipment and training. Translational Relevance EZ ratio may be employed in screening for angle closure glaucoma. It may also be helpful in outpatient medical clinic settings, where doctors need to judge the safety of topical or systemic pupil-dilating medications versus their risk of triggering acute angle closure glaucoma. Similarly, non ophthalmologists may use it to estimate the likelihood of acute angle closure glaucoma in emergency presentations.

Background: Development of a standardized internet-based system to self-assess skills in optic disc examination for glaucoma risk assessment. Design: Prospective internet-based observational study. Participants: Total of 197 participants (glaucoma subspecialists, general ophthalmologists and trainees) from 22 countries. Methods: Forty-two optic disc images demonstrating a range of features were selected from 2500 monoscopic disc photographs of normal and glaucomatous eyes. Images were presented to clinicians via website (http://www.gone-project.com). Participants were asked to assess nine topographic features and make a subjective assessment of glaucoma likelihood. Main Outcome Measures: Inter-observer agreement using kappa (κ) or weighted kappa (κw). Results: There was substantial level of inter-observer agreement between glaucoma subspecialists for assessment of glaucoma likelihood (κw = 0.63). Inter-observer agreement was high for haemorrhage (κ = 0.83) and substantial for disc size, disc shape, cup:disc ratio, peripapillary atrophy and cup shape (κw = 0.59–0.68). Subspecialists had stronger inter-observer agreement for glaucoma likelihood and for most disc characteristics than did trainees: the greatest difference being the assessment for retinal nerve fibre layer loss. Analysis of individual disc answers from ophthalmology trainees showed that discs leading to lower agreement of glaucoma likelihood tend to produce lower agreement for the assessment of cup:disc ratio, cup shape, cup depth and retinal nerve fibre layer. Discs with features of moderate to deep cup or cup:disc ratio between 0.6 and 0.8 also lead to lower agreement in glaucoma likelihood. Conclusions: This internet-based system is a readily accessible and standardized tool, for clinicians globally, that permits self-assessment and benchmarking of skills in optic disc examination.

We describe a model of acute intraocular pressure (IOP) elevation in the mouse eye that induces reversible loss of inner retinal function associated with oxidative stress, glial cell activation and minimal loss of retinal ganglion cell (RGC) number. Young healthy mouse eyes recover inner retinal function within 7-days but more persistent functional loss is seen in older mice. Manipulation of diet and exercise further modify RGC recovery demonstrating the utility of this injury model for investigating lifestyle and therapeutic interventions. We believe that systematic investigation into the characteristics and determinants of RGC recovery following an IOP challenge will shed light on processes that govern RGC vulnerability in the early stages of glaucoma.

To determine whether monoscopic vs stereoscopic viewing impacts evaluation of optic disc photographs for glaucoma diagnosis in an expert population.Prospective observational study.Twenty pairs of high-quality monoscopic and stereoscopic photographs of similar size and magnification (ie, 40 images), were selected to demonstrate a range of optic disc features from a total of 197 eyes of 197 patients with glaucoma and normal subjects recruited from a tertiary clinic. These were presented in randomized order via an interactive platform (http://stereo.gone-project.com/). Participants assessed 9 topographic features and estimated glaucoma likelihood for each photograph. Main outcome measures were intra- and inter-observer agreement.There was good intra-observer agreement between monoscopic and stereoscopic assessments of glaucoma likelihood (κw = 0.56). There was also good to substantial agreement for peripapillary atrophy (κw = 0.65), cup shape (κw = 0.65), retinal nerve fiber layer loss (κw = 0.69), vertical cup-to-disc ratio (κw = 0.58), and disc shape (κw = 0.57). However, intra-observer agreement was only fair to moderate for disc tilt, cup depth, and disc size (κw = 0.46-0.49). Inter-observer agreement for glaucoma likelihood in monoscopic photographs (κw = 0.61, 95% confidence interval [CI] = 0.55-0.67) was substantial and not lower than in stereoscopic photographs (κw = 0.59, CI = 0.54-0.65). Monoscopic photographs did not lead to lower levels of inter-observer agreement compared to stereoscopic photographs in the assessment of any optic disc characteristics, for example disc size (mono κw = 0.65, stereo κw = 0.52) and cup-to-disc ratio (mono κw = 0.72, stereo κw = 0.62).For expert observers in the evaluation of optic disc photographs for glaucoma likelihood, monoscopic optic disc photographs did not appear to represent a significant disadvantage compared to stereoscopic photographs.

PURPOSE: To determine the correlation between the perimetric outcomes from perimetry software Melbourne Rapid Fields (MRF) run on an Apple iPad tablet and those from the Humphrey Field Analyzer (HFA). METHODS: The MRF software was designed with features including variable fixation and fast thresholding using Bayes logic. Here, we report a cross-sectional study on 90 eyes from 90 participants: 12 had normal optic nerves and 78 had glaucoma with various degrees of visual field loss (41 mild and 37 moderate-severe). Exclusion criteria were patients with worse than 20/40 vision or recent intraocular surgery. The visual field outcomes of MRF were compared against those returned from the HFA 24-2 SITA standard. Participants were tested twice on the MRF to establish test-retest repeatability. RESULTS: The test durations were shorter on MRF than HFA (5.7 ± 0.1 vs. 6.3 ± 0.1 minutes, P < 0.001). MRF showed a high level of concordance in its outcomes with HFA (intraclass coefficient [ICC] = 0.93 for mean defect [MD] and 0.86 for pattern deviation [PD]) although the MRF tended to give a less negative MD (1.4 dB bias) compared with the HFA. MRF also showed levels of test-retest reliability comparable to HFA (ICC = 0.93 for MD and 0.89 for PD, 95% limits of agreement -4.5 to 4.3 dB). CONCLUSION: The perimetry results from the MRF have a strong correlation to the HFA outcomes. MRF also has test-retest reliability comparable to HFA. TRANSLATIONAL RELEVANCE: Portable tablet perimetry may allow accurate assessment of visual field when standard perimetry machines are unavailable or unsuitable.

Purpose Following the recent demonstration of increased mitochondrial DNA mutations in lymphocytes of POAG patients, the authors sought to characterize mitochondrial function in a separate cohort of POAG. Methods Using similar methodology to that previous applied to Leber's hereditary optic neuropathy (LHON) patients, maximal adenosine triphosphate (ATP) synthesis and cellular respiration rates, as well as cell growth rates in glucose and galactose media, were assessed in transformed lymphocytes from POAG patients (n = 15) and a group of age- and sex-matched controls (n = 15). Results POAG lymphoblasts had significantly lower rates of complex-I-driven ATP synthesis, with preserved complex-II-driven ATP synthesis. Complex-I driven maximal respiration was also significantly decreased in patient cells. Growth in galactose media, where cells are forced to rely on mitochondrial ATP production, revealed no significant differences between the control and POAG cohort. Conclusions POAG lymphoblasts in the study cohort exhibited a defect in complex-I of the oxidative phosphorylation pathway, leading to decreased rates of respiration and ATP production. Studies in LHON and other diseases have established that lymphocyte oxidative phosphorylation measurement is a reliable indicator of systemic dysfunction of this pathway. While these defects did not impact lymphoblast growth when the cells were forced to rely on oxidative ATP supply, the authors suggest that in the presence of a multitude of cellular stressors as seen in the early stages of POAG, these defects may lead to a bioenergetic crisis in retinal ganglion cells and an increased susceptibility to cell death.

Advancing age is a major risk factor for many neurodegenerative diseases but the underlying pathophysiology is not clear. We hypothesize that aging impairs the ability of neurons in the central nervous system to recover functionally after injury. To test this in retinal ganglion cells in vivo, we developed an optic nerve “stress test” which monitors the functional capacity of the optic nerve and retina, during and after a subischemic injury induced by intraocular pressure elevation. We report that older (18-month) C57BL/6J mice suffered greater loss of inner retinal function compared with younger adult mice following intraocular pressure (IOP) challenge. To investigate whether age-related vulnerability to IOP challenge can be modified, we subjected 12-month-old mice to dietary restriction (DR) (alternate-day fasting) for 6 months. Compared with age-matched ad libitum fed controls, DR mice showed greater recovery in inner retinal function following IOP challenge. DR was associated with reduced oxidative stress level following injury and improved mitochondrial oxidative phosphorylation enzyme activity compared with ad libitum controls. Taken together, this study provides in vivo evidence that DR improves functional recovery of the retina following injury and points to the potential benefits of therapies that target mitochondria for the protection of the aging retina and optic nerve against injury.

PURPOSE: The authors compared the visual gaze behaviors of glaucoma subspecialists with those of ophthalmology trainees during optic disc and retinal nerve fiber layer (RNFL) examination. METHODS: Seven glaucoma subspecialists and 23 ophthalmology trainees participated in the project. Participants were shown eight glaucomatous optic disc images with varied morphology. Eye movements during examination of the optic disc photographs were tracked. For each disc image, graders were asked to assign a presumptive diagnosis for probability of glaucoma. There was no time restriction. RESULTS: Overall, trainees spent more time looking at disc images than glaucoma subspecialists (21.3 [13.9-37.7] vs. 16.6 [12.7-19.7]) seconds; median [interquartile range (IQR)], respectively; P < 0.01) and had no systematic patterns of gaze behavior, and gaze behavior was unaltered by disc morphology or topographic cues of pathology. Experienced viewers demonstrated more systematic and ordered gaze behavior patterns and spent longer times observing areas with the greatest likelihood of pathology (superior and inferior poles of the optic nerve head and adjacent RNFL) compared with the trainees. For discs with focal pathology, the proportion of total time spent examining definite areas of pathology was 28.9% (22.4%-33.6%) for glaucoma subspecialists and 13.5% (12.2%-19.2%) for trainees (median [IQR]; P < 0.05). Furthermore, experts adapted their viewing habits according to disc morphology. CONCLUSIONS: Glaucoma subspecialists adopt systematic gaze behavior when examining the optic nerve and RNFL, whereas trainees do not. It remains to be elucidated whether incorporating systematic viewing behavior of the optic disc and RNFL into teaching programs for trainees may expedite their acquisition of accurate and efficient glaucoma diagnosis skills.

The similarities between glaucoma and mitochondrial optic neuropathies have driven a growing interest in exploring mitochondrial function in glaucoma. The specific loss of retinal ganglion cells is a common feature of mitochondrial diseases - not only the classic mitochondrial optic neuropathies of Leber's Hereditary Optic Neuropathy and Autosomal Dominant Optic Atrophy - but also occurring together with more severe central nervous system involvement in many other syndromic mitochondrial diseases. The retinal ganglion cell, due to peculiar structural and energetic constraints, appears acutely susceptible to mitochondrial dysfunction. Mitochondrial function is also well known to decline with aging in post-mitotic tissues including neurons. Because age is a risk factor for glaucoma this adds another impetus to investigating mitochondria in this common and heterogeneous neurodegenerative disease. Mitochondrial function may be impaired by either nuclear gene or mitochondrial DNA genetic risk factors, by mechanical stress or chronic hypoperfusion consequent to the commonly raised intraocular pressure in glaucomatous eyes, or by toxic xenobiotic or even light-induced oxidative stress. If primary or secondary mitochondrial dysfunction is further established as contributing to glaucoma pathogenesis, emerging therapies aimed at optimizing mitochondrial function represent potentially exciting new clinical treatments that may slow retinal ganglion cell and vision loss in glaucoma.

PURPOSE. To prospectively evaluate the effect of 1.25 mg and 2.5 mg intracameral bevacizumab on surgical outcomes of trabeculectomy for neovascular glaucoma (NVG), with primary outcome measures being the regression of neovascularization of iris (NVI) and reduction of intraocular pressure (IOP). METHODS. Consecutive patients with neovascular glaucoma from December 2006 to March 2007 were randomized into two cohorts assigned to receive 1.25 mg (Group 1) or 2.5 mg (Group 2) intracameral bevacizumab prior to undergoing mitomycin C (MMC) trabeculectomy. Surgical outcome measures were evaluated following initial injection and during follow-up post-surgery. RESULTS. The most common causes for iris neovascularization were central retinal vein occlusion (47.3%) and proliferative diabetic retinopathy (36.8%). Following intracameral bevacizumab, there was a reduction in IOP compared to baseline in both treatment groups (Group 1, n=9: –10.4±4.5 mmHg, p=0.57; Group 2, n=10: –12.1±5.5 mmHg, p=0.1). The reduction in IOP was not statistically significant between the two groups (p=0.55). None of the eyes underwent further retinal ablation post trabeculectomy. Reappearance of NVI was seen in three eyes (Group 1, n=2; Group 2, n=1) after 3 months. There was no statistically significant difference in regression of NVI grade between the treatment groups (p=0.1). CONCLUSIONS. The efficacy of an intracameral dose of 2.5 mg of bevacizumab prior to trabeculectomy for eyes with NVG is not significantly different from a 1.25 mg dose. Intracameral bevacizumab followed by trabeculectomy results in good surgical outcomes. Longer follow-up would be needed to evaluate differences in recurrence rates of iris neovascularization using different dosages. (Eur J Ophthalmol 2009; 19: 435-41)

Glaucoma is increasingly recognized as a neurodegenerative disorder, characterized by the accelerated loss of retinal ganglion cells (RGCs) and their axons. Open angle glaucoma prevalence and incidence increase exponentially with increasing age, yet the pathophysiology underlying increasing age as a risk factor for glaucoma is not well understood. Accumulating evidence points to age-related mitochondrial dysfunction playing a key role in the etiology of other neurodegenerative disorders including amyotrophic lateral sclerosis, Alzheimer and Parkinson disease. The 2 major functions of mitochondria are the generation of ATP through oxidative phosphorylation and the regulation of cell death by apoptosis. This review details evidence to support our hypothesis that age-associated mitochondrial dysfunction renders RGCs susceptible to glaucomatous injury by reducing the energy available for repair processes and predisposing RGCs to apoptosis. Eliciting the role of mitochondria in glaucoma pathogenesis may uncover novel therapeutic targets for protecting the optic nerve and preventing vision loss in glaucoma.

IMPORTANCE: Glaucoma is a significant health problem for which diagnosis remains suboptimal. Optic disc evaluation, which is fundamental to the diagnosis, is a difficult skill to acquire. OBJECTIVES: To determine the optic disc characteristics that most influence decision making in the assessment of glaucoma likelihood and to ascertain the optic disc features associated with overestimation and underestimation of glaucoma likelihood. DESIGN, SETTING, AND PARTICIPANTS: This prospective, observational, Internet-based study with multinational participation included 197 ophthalmic clinicians (37 glaucoma subspecialists, 51 comprehensive ophthalmologists, and 109 ophthalmology trainees) from 22 countries who self-registered for the Glaucomatous Optic Neuropathy Evaluation (GONE) Project from December 1, 2008 through June 30, 2010. INTERVENTIONS: A series of 42 monoscopic optic disc photographs of healthy and glaucomatous eyes were presented to clinicians using the GONE Project Program. Participants were asked to assess each disc according to 9 conventional topographic features and assign a presumptive grade for glaucoma likelihood. MAIN OUTCOMES AND MEASURES: Agreement (κ and weighted κ) among participants for disc signs and glaucoma likelihood and contributions of disc-related factors to overestimation and underestimation of glaucoma likelihood. RESULTS: Ophthalmology trainees and comprehensive ophthalmologists underestimated glaucoma likelihood in a mean (SD) of 22.1% (1.6%) and 23.8% (1.8%) of discs, respectively. Underestimation of vertical cup-disc ratio and failure to identify retinal nerve fiber layer loss, disc hemorrhage, or rim loss were most likely to lead to underestimation of glaucoma. When all 4 features were inaccurately assessed, underestimation of glaucoma likelihood increased to 43.0%. Ophthalmology trainees and comprehensive ophthalmologists overestimated glaucoma likelihood in a mean (SD) of 13.0% (1.2%) and 8.9% (1.3%) of discs, respectively. Overestimation of glaucoma likelihood was associated with overestimation of retinal nerve fiber layer loss, rim loss, vertical cup-disc ratio, disc hemorrhage, and incorrect assessment of disc tilt and was more likely in large discs. CONCLUSIONS AND RELEVANCE: Ophthalmology trainees and comprehensive ophthalmologists underestimated glaucoma likelihood in approximately 1 in 5 disc photographs and were twice as likely to underestimate as overestimate glaucoma likelihood. Underestimating the vertical cup-disc ratio and cup shape and missing retinal nerve fiber layer defects and disc hemorrhage were the key errors that led to underestimation. When all 4 parameters were incorrectly assessed, underestimation increased to almost 1 in 2.